@article{d228250ef1794a6fa15ca5d353cd16db,
title = "A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission",
abstract = "The ESCRT complexes drive membrane scission in HIV-1 release, autophagosome closure, multivesicular body biogenesis, cytokinesis, and other cell processes. ESCRT-I is the most upstream complex and bridges the system to HIV-1 Gag in virus release. The crystal structure of the headpiece of human ESCRT-I comprising TSG101–VPS28–VPS37B–MVB12A was determined, revealing an ESCRT-I helical assembly with a 12-molecule repeat. Electron microscopy confirmed that ESCRT-I subcomplexes form helical filaments in solution. Mutation of VPS28 helical interface residues blocks filament formation in vitro and autophagosome closure and HIV-1 release in human cells. Coarse-grained (CG) simulations of ESCRT assembly at HIV-1 budding sites suggest that formation of a 12-membered ring of ESCRT-I molecules is a geometry-dependent checkpoint during late stages of Gag assembly and HIV-1 budding and templates ESCRT-III assembly for membrane scission. These data show that ESCRT-I is not merely a bridging adaptor; it has an essential scaffolding and mechanical role in its own right.",
author = "Flower, {Thomas G.} and Yoshinori Takahashi and Arpa Hudait and Kevin Rose and Nicholas Tjahjono and Pak, {Alexander J.} and Yokom, {Adam L.} and Xinwen Liang and Wang, {Hong Gang} and Fadila Bouamr and Voth, {Gregory A.} and Hurley, {James H.}",
note = "Funding Information: We thank B. Yang for contributing to early stages of this project, S. Fromm, C. Buffalo, and P. Grob for electron microscopy advice and support, K. Larsen for comments on the manuscript, and J. Briggs for providing immature Gag lattice maps. This work was supported by NIH grants R37 AI112442 (J.H.H.), R01 GM127954 (H.G.W), R01 GM128507 (A.H. and G.A.V.) and F32 AI150477 (A.J.P.). Beamline 8.3.1 at the Advanced Light Source is supported by the National Institutes of Health (R01 GM124149 and P30 GM124169), Plexxikon Inc., and the Integrated Diffraction Analysis Technologies program of the US Department of Energy Office of Biological and Environmental Research. The Advanced Light Source (Berkeley, CA) is a national user facility operated by Lawrence Berkeley National Laboratory on behalf of the US Department of Energy under contract number DE-AC02-05CH11231, Office of Basic Energy Sciences. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = jun,
day = "1",
doi = "10.1038/s41594-020-0426-4",
language = "English (US)",
volume = "27",
pages = "570--580",
journal = "Nature Structural Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "6",
}
